TY - JOUR
T1 - Improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis B vaccine containing pre-S1 and pre-S2 antigens as compared with conventional yeast-derived vaccines
AU - Shouval, D.
AU - Ilan, Y.
AU - Adler, R.
AU - Deepen, R.
AU - Panet, A.
AU - Even-Chen, Z.
AU - Gorecki, M.
AU - Gerlich, W. H.
PY - 1994
Y1 - 1994
N2 - The widely used hepatitis B virus (HBV) vaccines consist of the small hepatitis B surface (SHBs) protein produced in transfected yeast cells. The frequency of non-responders, especially among immunocompromised patients, has increased the demand for a more immunogenic vaccine. We evaluated the immunogenicity of recombinant HBs 20 nm particles secreted by transfected Chinese hamster ovary (CHO) cells. Bio-Hep-B (BioTechnology General Ltd, Israel), and compared it with yeast-derived vaccines. The CHO-derived vaccine contains the small hepatitis B surface antigen (SHBs protein) as the major component, as well as the middle HBs (MHBs, pre-S2) and the large HBs (LHBs, pre-S1) antigens. Nine groups of ten female Balb/c mice, 4-6 weeks old, were injected once intraperitoneally (i.p.) with 0.09, 0.27 or 0.81 μg of each of three vaccines: Bio-Hep-B or two conventional yeast-derived recombinant vaccines, Engerix-B (SmithKline Beecham, Belgium) and H-B-Vax II (Merck, Sharp & Dohme, USA) containing only non-glycosylated SHBs antigen. After 30 days, 40% of the mice injected with 0.09 μg Bio- Hep-B had seroconverted, but none of the mice receiving the same dose of the other vaccines. The immunogenic dose in 50% of the mice at day 14 after injection was 0.13 μg for Bio-Hep-B, but over 0.81 μg for the other two vaccines. Mice of the strain B10/M (which are unresponsive to SHBs and MHBs antigens at the T-cell level) developed 100-fold higher anti-HBs titres after immunization with 1 μg of Bio-Hep-B i.p., as compared with mice receiving the same amount of yeast-derived HBsAg vaccines. Antibodies to sequential LHBs and MHBs antigens were detected in mice or rabbits immunized with Bio-Hep-B, but not in mice injected with the other SHBs vaccines. These results indicate that the new recombinant vaccine, produced from CHO cells transfected with HBV DNA encoding for all three HBs antigens, elicits an augmented anti-HBs response in mice as compared with mice receiving the currently used yeast-derived vaccines. It remains to be seen whether the enhanced seroconversion rate and anti-HBs titres induced by this vaccine in mice will be of benefit in humans and will increase efficacy and prolong the duration of protection against HBV.
AB - The widely used hepatitis B virus (HBV) vaccines consist of the small hepatitis B surface (SHBs) protein produced in transfected yeast cells. The frequency of non-responders, especially among immunocompromised patients, has increased the demand for a more immunogenic vaccine. We evaluated the immunogenicity of recombinant HBs 20 nm particles secreted by transfected Chinese hamster ovary (CHO) cells. Bio-Hep-B (BioTechnology General Ltd, Israel), and compared it with yeast-derived vaccines. The CHO-derived vaccine contains the small hepatitis B surface antigen (SHBs protein) as the major component, as well as the middle HBs (MHBs, pre-S2) and the large HBs (LHBs, pre-S1) antigens. Nine groups of ten female Balb/c mice, 4-6 weeks old, were injected once intraperitoneally (i.p.) with 0.09, 0.27 or 0.81 μg of each of three vaccines: Bio-Hep-B or two conventional yeast-derived recombinant vaccines, Engerix-B (SmithKline Beecham, Belgium) and H-B-Vax II (Merck, Sharp & Dohme, USA) containing only non-glycosylated SHBs antigen. After 30 days, 40% of the mice injected with 0.09 μg Bio- Hep-B had seroconverted, but none of the mice receiving the same dose of the other vaccines. The immunogenic dose in 50% of the mice at day 14 after injection was 0.13 μg for Bio-Hep-B, but over 0.81 μg for the other two vaccines. Mice of the strain B10/M (which are unresponsive to SHBs and MHBs antigens at the T-cell level) developed 100-fold higher anti-HBs titres after immunization with 1 μg of Bio-Hep-B i.p., as compared with mice receiving the same amount of yeast-derived HBsAg vaccines. Antibodies to sequential LHBs and MHBs antigens were detected in mice or rabbits immunized with Bio-Hep-B, but not in mice injected with the other SHBs vaccines. These results indicate that the new recombinant vaccine, produced from CHO cells transfected with HBV DNA encoding for all three HBs antigens, elicits an augmented anti-HBs response in mice as compared with mice receiving the currently used yeast-derived vaccines. It remains to be seen whether the enhanced seroconversion rate and anti-HBs titres induced by this vaccine in mice will be of benefit in humans and will increase efficacy and prolong the duration of protection against HBV.
KW - Hepatitis B virus immunization
KW - pre-S antigen
KW - pre-S antigen
UR - http://www.scopus.com/inward/record.url?scp=0028172936&partnerID=8YFLogxK
U2 - 10.1016/0264-410X(94)90155-4
DO - 10.1016/0264-410X(94)90155-4
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C2 - 7533967
AN - SCOPUS:0028172936
SN - 0264-410X
VL - 12
SP - 1453
EP - 1459
JO - Vaccine
JF - Vaccine
IS - 15
ER -
